The common interests of the Neuro-oncology Program are primary malignant brain tumors of adults and children. The scientific goals are: Aim 1: to conduct epidemiological and molecular epidemiological studies to invesfigate efiology and to identify populafions at greater and lesser risk for development of malignant brain tumors in adults and children; Aim 2: to determine molecular mechanisms of transformafion, altered growth control, and invasion of malignant brain tumors of adults and children; Aim 3: to identify new drugs active against primary brain tumors of adults and children, to determine mechanisms of drug resistance in primary brain tumors, and to institute methods to overcome drug resistance; Aim 4: to develop monoclonal antibodies and recombinant DNA anfibody fragments reactive with molecular targets, primary brain tumors, and to develop immunoconjugates for brain tumor treatment; Aim 5: to develop new radiolabeling technology for peptides and monoclonal antibodies and their fragments that will facilitate the invesfigafion of promising radionuclides, including the a-emitter ^Astafine and the p-emitter ^''''Lutetium, in targeted radiotherapy clinical trial for brain tumor patients; Aim 6: to develop cell-mediated immunotherapy and dendritic-based vaccine trials for brain tumors; Aim 7: to develop oncolytic poliovirus with no neurovirulence, but retention of oncolytic capacity for gliomas, into a reagent that can be used for therapy of malignant gliomas and neoplastic meningifis from breast cancer; Aim 8: to develop imaging capabilifies with Positron Emission Tomography (PET) for improved brain tumor diagnosis, monitoring of therapeutic response, and determinafion of pafient-specific radiafion dosimetry in radiolabeled anfibody, chemotherapy and small molecular inhibitor clinical trials in brain tumor patients; Aim 9: to design and execute Phase I, Phase 11, and Phase 111 clinical trials in primary and metastafic brain tumors in adults and children, based on laboratory discoveries within the Program, and to execute clinical trials for improvement of quality of life in brain tumor pafients. The Program includes 26 members from 12 basic and clinical departments within Duke University. Total funding for program members is $18,693,484, of which $10,458,928 is from peer- reviewed sources. A cancer focus is illustrated by $5,092,026 or 48.7% of funding from the NCI, the American Cancer Society or the Department of Defense. From 2004-2008, program members published 612 papers in peer-reviewed journals cited in PubMed. Of these publications, 20% are the result of intra-programmatic collaborafions and 27% due to inter-programmafic collaborafions.